Benefits of oxytocin administration in obstructive sleep apnea
Activation of oxytocin receptors has shown benefits in animal models of obstructive sleep apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. Eight patients diagnosed with OSA were administered intranasal oxytocin (40 IU). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability, were assessed. Oxytocin significantly increased indexes of parasympathetic activity, including heart rate variability, total sleep time, and the postpolysommogram sleep assessment score...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Jain, V., Marbach, J., Kimbro, S., Andrade, D. C., Jain, A., Capozzi, E., Mele, K., Del Rio, R., Kay, M. W., Mendelowitz, D. Tags: RESEARCH ARTICLE Source Type: research

TGF-{beta} inhibits alveolar protein transport by promoting shedding, regulated intramembrane proteolysis, and transcriptional downregulation of megalin
Disruption of the alveolar-capillary barrier is a hallmark of acute respiratory distress syndrome (ARDS) that leads to the accumulation of protein-rich edema in the alveolar space, often resulting in comparable protein concentrations in alveolar edema and plasma and causing deleterious remodeling. Patients who survive ARDS have approximately three times lower protein concentrations in the alveolar edema than nonsurvivors; thus the ability to remove excess protein from the alveolar space may be critical for a positive outcome. We have recently shown that clearance of albumin from the alveolar space is mediated by megalin, a...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Mazzocchi, L. C., Vohwinkel, C. U., Mayer, K., Herold, S., Morty, R. E., Seeger, W., Vadasz, I. Tags: RESEARCH ARTICLE Source Type: research

Repetitive intradermal bleomycin injections evoke T-helper cell 2 cytokine-driven pulmonary fibrosis
In this study, using a novel repetitive intradermal bleomycin model in which mice develop extensive lung fibrosis and a progressive decline in lung function compared with saline-treated control mice, we investigated profibrotic functions of Th2 cytokines. To determine the role of IL-13 signaling in the pathogenesis of bleomycin-induced pulmonary fibrosis, wild-type, IL-13, and IL-4Rα-deficient mice were treated with bleomycin, and lungs were assessed for changes in lung function and pulmonary fibrosis. Histological staining and lung function measurements demonstrated that collagen deposition and lung function decline...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Singh, B., Kasam, R. K., Sontake, V., Wynn, T. A., Madala, S. K. Tags: RESEARCH ARTICLE Source Type: research

FGF9 prevents pleural fibrosis induced by intrapleural adenovirus injection in mice
Fibroblast growth factor 9 (FGF9) is necessary for fetal lung development and is expressed by epithelium and mesothelium. We evaluated the role of FGF9 overexpression on adenoviral-induced pleural injury in vivo and determined the biological effects of FGF9 on mesothelial cells in vitro. We assessed the expression of FGF9 and FGF receptors by mesothelial cells in both human and mouse lungs. Intrapleural injection of an adenovirus expressing human FGF9 (AdFGF9) or a control adenovirus (AdCont) was performed. Mice were euthanized at days 3, 5, and 14. Expression of FGF9 and markers of inflammation and myofibroblastic differe...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Justet, A., Joannes, A., Besnard, V., Marchal-Somme, J., Jaillet, M., Bonniaud, P., Sallenave, J. M., Solhonne, B., Castier, Y., Mordant, P., Mal, H., Cazes, A., Borie, R., Mailleux, A. A., Crestani, B. Tags: RESEARCH ARTICLE Source Type: research

Lethal avian influenza A (H5N1) virus induces ataxic breathing in mice with apoptosis of pre-Botzinger complex neurons expressing neurokinin-1 receptor
Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 days postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NK1R), which is the respiratory rhythm generator, have not been explored. Body temperature, weight, ventilation, and arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483, and nonlethal HK486 viral-infected mice. Immunoreactivities (IR) of PBC NK1R, H5N1 viral nucleoprotein (NP), and active caspase-3 (CASP3; a marker for a...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Zhuang, J., Zang, N., Ye, C., Xu, F. Tags: RESEARCH ARTICLE Source Type: research

X-ray-based lung function measurement reveals persistent loss of lung tissue elasticity in mice recovered from allergic airway inflammation
Chronic asthma patients experience difficulties even years after the inciting allergen. Although studies in small animal asthma models have enormously advanced progress in uncovering the mechanisms of inception and development of the disease, little is known about the processes involved in the persistence of asthma symptoms in the absence of allergen exposure. Long-term asthma mouse models have so far been scarce or not been able to reproduce the findings in patients. Here we used a common ovalbumin-induced acute allergic airway inflammation mouse model to study lung function and remodeling after a 4-mo recovery period. We...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Markus, M. A., Borowik, S., Reichardt, M., Tromba, G., Alves, F., Dullin, C. Tags: RESEARCH ARTICLE Source Type: research

Transglutaminase 2 in pulmonary and cardiac tissue remodeling in experimental pulmonary hypertension
We report here that TG2 expression and activity as measured by serotonylated fibronectin and protein cross-linking activity along with fibrogenic markers are significantly elevated in lungs and right ventricles of SuHypoxic mice with PH. Similarly, TG2 expression and activity, protein cross-linking activity, and fibrogenic markers are significantly increased in cultured cardiac and pulmonary artery adventitial fibroblasts in response to hypoxia exposure. Pharmacological inhibition of TG2 activity with ERW1041E significantly reduced hypoxia-induced cross-linking activity and synthesis of collagen 1 and α-smooth muscle...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Penumatsa, K. C., Toksoz, D., Warburton, R. R., Kharnaf, M., Preston, I. R., Kapur, N. K., Khosla, C., Hill, N. S., Fanburg, B. L. Tags: RESEARCH ARTICLE Source Type: research

Importance of kynurenine in pulmonary hypertension
The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hypertension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to investigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine, and kynurenic acid levels were measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls, and 20 patients with chronic lung disease or metabolic syndrome without PH. Laser-dissected pulmonary arteries from IPAH and control lungs were tested for the expression of indoleamine-2, 3-dioxygenase (IDO), the rate-limiting enzyme for the conversion ...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Nagy, B. M., Nagaraj, C., Meinitzer, A., Sharma, N., Papp, R., Foris, V., Ghanim, B., Kwapiszewska, G., Kovacs, G., Klepetko, W., Pieber, T. R., Mangge, H., Olschewski, H., Olschewski, A. Tags: RESEARCH ARTICLE Source Type: research

LungMAP: The Molecular Atlas of Lung Development Program
The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infan...
Source: AJP: Lung Cellular and Molecular Physiology - November 1, 2017 Category: Respiratory Medicine Authors: Ardini-Poleske, M. E., Clark, R. F., Ansong, C., Carson, J. P., Corley, R. A., Deutsch, G. H., Hagood, J. S., Kaminski, N., Mariani, T. J., Potter, S. S., Pryhuber, G. S., Warburton, D., Whitsett, J. A., Palmer, S. M., Ambalavanan, N., The LungMAP Consort Tags: REVIEW Source Type: research

Distinct PKA regulatory subunits mediate PGE2 inhibition of TGF{beta}-1-stimulated collagen I translation and myofibroblast differentiation
Prostaglandin E2 (PGE2), via cAMP signaling, inhibits a variety of fibroblast functions relevant to fibrogenesis. Among these are their translation of collagen I protein and their differentiation to myofibroblasts. PKA is central to these actions, with cAMP binding to regulatory (R) subunits leading to the release of catalytic subunits. Here we examined the role of specific PKAR subunit isoforms in these inhibitory actions in transforming growth factor β-1 (TGFβ-1)-stimulated human lung fibroblasts (HLFs). HLFs expressed all four R subunit isoforms. siRNA-mediated knockdown of subunits PKARIα and PKARII&alp...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Wettlaufer, S. H., Penke, L. R., Okunishi, K., Peters-Golden, M. Tags: RESEARCH ARTICLE Source Type: research

Effects of prostaglandin lipid mediators on agonist-induced lung endothelial permeability and inflammation
This study compared effects of PGE2, PGI2, PGF2α, PGA2, PGJ2, and PGD2 on human pulmonary EC. EC permeability was assessed by measurements of transendothelial electrical resistance and cell monolayer permeability for FITC-labeled tracer. Anti-inflammatory effects of PGs were evaluated by analysis of expression of adhesion molecule ICAM1 and secretion of soluble ICAM1 and cytokines by EC. PGE2, PGI2, and PGA2 exhibited the most potent barrier-enhancing effects and most efficient attenuation of thrombin-induced EC permeability and contractile response, whereas PGI2 effectively suppressed thrombin-induced permeability b...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Ke, Y., Oskolkova, O. V., Sarich, N., Tian, Y., Sitikov, A., Tulapurkar, M. E., Son, S., Birukova, A. A., Birukov, K. G. Tags: RESEARCH ARTICLE Source Type: research

Mitochondrial quality control in alveolar epithelial cells damaged by S. aureus pneumonia in mice
We report that apart from cell lysis by direct contact with microbes, modest epithelial cell death was detected despite significant mitochondrial damage. Cell death by TdT-mediated dUTP nick-end labeling staining occurred on days 1 and 2 postinoculation: apoptosis shown by caspase-3 cleavage was present on days 1 and 2, while necroptosis shown by increased levels of phospho- mixed lineage kinase domain-like protein (MLKL) and receptor-interacting serine/threonine-protein kinase 1 (RIPK1) was present on day 1. Cell death in alveolar type I (AT1) cells assessed by bronchoalveolar lavage fluid receptor for advanced glycation ...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Suliman, H. B., Kraft, B., Bartz, R., Chen, L., Welty-Wolf, K. E., Piantadosi, C. A. Tags: RESEARCH ARTICLE Source Type: research

Role of LTBP4 in alveolarization, angiogenesis, and fibrosis in lungs
Deficiency of the extracellular matrix protein latent transforming growth factor-β (TGF-β)-binding protein-4 (LTBP4) results in lack of intact elastic fibers, which leads to disturbed pulmonary development and lack of normal alveolarization in humans and mice. Formation of alveoli and alveolar septation in pulmonary development requires the concerted interaction of extracellular matrix proteins, growth factors such as TGF-β, fibroblasts, and myofibroblasts to promote elastogenesis as well as vascular formation in the alveolar septae. To investigate the role of LTBP4 in this context, lungs of LTBP4-deficient ...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Bultmann-Mellin, I., Dinger, K., Debuschewitz, C., Loewe, K. M. A., Melcher, Y., Plum, M. T. W., Appel, S., Rappl, G., Willenborg, S., Schauss, A. C., Jüngst, C., Krüger, M., Dressler, S., Nakamura, T., Wempe, F., Alejandre Alcazar, M. A., Tags: RESEARCH ARTICLE Source Type: research

Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes
Macrolides antibiotics have been effectively used in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were ...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Fan, L.-C., Lin, J.-L., Yang, J.-W., Mao, B., Lu, H.-W., Ge, B.-X., Choi, A. M. K., Xu, J.-F. Tags: RESEARCH ARTICLE Source Type: research

Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics
We explored whether the proteomic analysis of exhaled breath condensate (EBC) may provide biomarkers for noninvasive screening for the early detection of lung cancer (LC). EBC was collected from 192 individuals [49 control (C), 49 risk factor-smoking (S), 46 chronic obstructive pulmonary disease (COPD) and 48 LC]. With the use of liquid chromatography and tandem mass spectrometry, 348 different proteins with a different pattern among the four groups were identified in EBC samples. Significantly more proteins were identified in the EBC from LC compared with other groups (C: 12.4 ± 1.3; S: 15.3 ± 1; COPD: 14 &p...
Source: AJP: Lung Cellular and Molecular Physiology - October 1, 2017 Category: Respiratory Medicine Authors: Lopez-Sanchez, L. M., Jurado-Gamez, B., Feu-Collado, N., Valverde, A., Canas, A., Fernandez-Rueda, J. L., Aranda, E., Rodriguez-Ariza, A. Tags: RESEARCH ARTICLE Source Type: research